The objective of this project is to analyze the origins and course of diabetic microangiopathy of the retina in order to effect a better understanding for prevention of vascular changes in diabetics. This will be accomplished by: (a) determining the systemic comparative pathology of microangiopathy in both humans and experimentally induced diabetic animals, by means of histocytochemical and ultrastructural studies; (b) studying the vasuclar abnormalities of EMC virus-induced diabetic animal models, particularly in the retina and brain, compared to chemically induced diabetic animals. This includes study of the basement membranes of the capillaries, looking at lesions in the membranes, substructural changes of proliferating tropocollagen-like materials, and disruption of the blood-retinal-barrier. These findings will be compared with microangiopathy of the brain; (c) testing the effects on normal and diabetic blood vessel explants in culture media with and without diabetic serum, lactic acid, alpha-2-macroglobulin, and other potentially significant biochemical modulations; (d) examining the possible correlations between hypertension and the high incidence of atherosclerosis in association with nodular glomerulosclerosis in diabetics--Kimmelstiel-Wilson syndrome--using diabetic animals with experimentally induced renal hypertension.